OBJECTIVE: To investigate the anti-inflammatory effect of rutaecarpine (RUT) on monosodium urate crystal (MSU)-induced murine peritonitis in mice and further explored the underlying mechanism of RUT in lipopolysaccharide (LPS)/MSU-induced gout model in vitro. METHODS: In MSU-induced mice, 36 male C57BL/6 mice were randomly divided into 6 groups of 8 mice each group, including the control group, model group, RUT low-, medium-, and high-doses groups, and prednisone acetate group. The mice in each group were orally administered the corresponding drugs or vehicle once a day for 7 consecutive days. The gout inflammation model was established by intraperitoneal injection of MSU to evaluate the anti-gout inflammatory effects of RUT. Then the proinflammatory cytokines were measured by enzyme-linked immunosorbent assay (ELISA) and the proportions of infiltrating neutrophils cytokines were detected by flow cytometry. In LPS/MSU-treated or untreated THP-1 macrophages, cell viability was observed by cell counting kit 8 and proinflammatory cytokines were measured by ELISA. The percentage of pyroptotic cells were detected by flow cytometry. Respectively, the mRNA and protein levels were measured by real-time quantitative polymerase chain reaction (qRT-PCR) and Western blot, the nuclear translocation of nuclear factor κB (NF-κB) p65 was observed by laser confocal imaging. Additionally, surface plasmon resonance (SPR) and molecular docking were applied to validate the binding ability of RUT components to tumor necrosis factor α (TNF-α) targets. RESULTS: RUT reduced the levels of infiltrating neutrophils and monocytes and decreased the levels of the proinflammatory cytokines interleukin 1β (IL-1β) and interleukin 6 (IL-6, all P<0.01). In vitro, RUT reduced the production of IL-1β, IL-6 and TNF-α. In addition, RT-PCR revealed the inhibitory effects of RUT on the mRNA levels of IL-1β, IL-6, cyclooxygenase-2 and TNF-α (P<0.05 or P<0.01). Mechanistically, RUT markedly reduced protein expressions of tumor necrosis factor receptor (TNFR), phospho-mitogen-activated protein kinase (p-MAPK), phospho-extracellular signal-regulated kinase, phospho-c-Jun N-terminal kinase, phospho-NF-κB, phospho-kinase α/β, NOD-like receptor thermal protein domain associated protein 3 (NLRPS), cleaved-cysteinyl aspartate specific proteinase-1 and cleaved-gasdermin D in macrophages (P<0.05 or P<0.01). Molecularly, SPR revealed that RUT bound to TNF-α with a calculated equilibrium dissociation constant of 31.7 µmol/L. Molecular docking further confirmed that RUT could interact directly with the TNF-α protein via hydrogen bonding, van der Waals interactions, and carbon-hydrogen bonding. CONCLUSION RUT alleviated MSU-induced peritonitis and inhibited the TNFR1-MAPK/NF-κB and NLRP3 inflammasome signaling pathway to attenuate gouty inflammation induced by LPS/MSU in THP-1 macrophages, suggesting that RUT could be a potential therapeutic candidate for gout.
Animals ; NF-kappa B/metabolism* ; Male ; Indole Alkaloids/therapeutic use* ; Signal Transduction/drug effects* ; Mice, Inbred C57BL ; Inflammation/complications* ; Uric Acid ; Quinazolines/therapeutic use* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Humans ; Gout/chemically induced* ; Inflammasomes/metabolism* ; Cytokines/metabolism* ; THP-1 Cells ; Mitogen-Activated Protein Kinases/metabolism* ; Mice ; Molecular Docking Simulation ; Lipopolysaccharides ; Quinazolinones

Adenoid cystic carcinoma is a malignant tumor of the head and neck, this article reports a case of a large adenoid cystic carcinoma of the skull base, with the lesion involving the sphenoid sinus, sphenoid bone wings, pterygopalatine fossa, nfratemporal fossa, hard palate, and other structures. The treatment plan consisted of surgical excision, primary reconstrction of the surgical defect,and postoperative radiotherapy, resulting in a favorable prognosis for the patient.
Humans ; Carcinoma, Adenoid Cystic/surgery* ; Maxillary Sinus/surgery* ; Maxillary Sinus Neoplasms/surgery* ; Palate, Hard/surgery* ; Skull Base Neoplasms/surgery* ; Surgical Flaps

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients′suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aims to establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. TMJ disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.

Objective To evaluate the bioequivalence and safety of ezetimibe tablets in healthy Chinese subjects.Methods The study was designed as a single-center,randomized,open-label,two-period,two-way crossover,single-dose trail.Subjects who met the enrollment criteria were randomized into fasting administration group and postprandial administration group and received a single oral dose of 10 mg of the subject presparation of ezetimibe tablets or the reference presparation per cycle.The blood concentrations of ezetimibe and ezetimibe-glucuronide conjugate were measured by high-performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS),and the bioequivalence of the 2 preparations was evaluated using the WinNonlin 7.0 software.Pharmacokinetic parameters were calculated to evaluate the bioequivalence of the 2 preparations.The occurrence of all adverse events was also recorded to evaluate the safety.Results The main pharmacokinetic parameters of total ezetimibe in the plasma of the test and the reference after a single fasted administration:Cmax were(118.79±35.30)and(180.79±51.78)nmol·mL-1;tmax were 1.40 and 1.04 h;t1/2 were(15.33±5.57)and(17.38±7.24)h;AUC0-t were(1 523.90±371.21)and(1 690.99±553.40)nmol·mL-1·h;AUC0-∞ were(1 608.70±441.28),(1 807.15±630.00)nmol·mL-1·h.The main pharmacokinetic parameters of total ezetimibe in plasma of test and reference after a single meal:Cmax were(269.18±82.94)and(273.93±87.78)nmol·mL-1;Tmax were 1.15 and 1.08 h;t1/2 were(22.53±16.33)and(16.02±5.84)h;AUC0_twere(1 463.37±366.03),(1 263.96±271.01)nmol·mL-1·h;AUC0-∞ were(1 639.01±466.53),(1 349.97±281.39)nmol·mL-1·h.The main pharmacokinetic parameters Cmax,AUC0-tand AUC0-∞ of the two preparations were analyzed by variance analysis after logarithmic transformation.In the fasting administration group,the 90％CI of the log-transformed geometric mean ratios were within the bioequivalent range for the remaining parameters in the fasting dosing group,except for the Cmax of ezetimibe and total ezetimibe,which were below the lower bioequivalent range.The Cmax of ezetimibe,ezetimibe-glucuronide,and total ezetimibe in the postprandial dosing group was within the equivalence range,and the 90％CI of the remaining parameters were not within the equivalence range for bioequivalence.Conclusion This test can not determine whether the test preparation and the reference preparation of ezetimibe tablets have bioequivalence,and further clinical trials are needed to verify it.

Objective To establish the finite element model of spinal canal reconstruction and internal fixation,analysis influence of spinal canal reconstruction and internal fixation on spinal stability,and verify the effectiveness and reliability of spinal canal reconstruction and internal fixation in spinal canal surgery.Methods A 30-year-old male healthy volunteer with a height of 172 cm and weight of 75 kg was selected and his lumbar CT data were collected to establish a finite element model of normal lumbar Lo3-L,and the results were compared with in vitro solid results and published finite element analysis results to verify the validity of the model.They were divided into normal group,laminectomy group and spinal canal reconstruction group according to different treatment methods.Under the same boundary fixation and physiological load conditions,six kinds of ac-tivities were performed,including forward bending,backward extension,left bending,right bending,left rotation and right rota-tion,and the changes of range of motion(ROM)of L3-L4,L4-L5 segments and overall maximum ROM of L3-L5 were analyzed under the six conditions.Results The ROM displacement range of each segment of the constructed L3-L5 finite element model was consistent with the in vitro solid results and previous literature data,which confirms the validity of the model.In L3-L4,ROM of spinal canal reconstruction group was slightly increased than that of normal group during posterior extension(＞5％dif-ference),and ROM of other conditions was similar to that of normal group(＜5％difference).ROM in laminectomy group was significantly increase than that in normal group and spinal canal reconstruction group under the condition of flexion,extension,left and right rotation.In L4-L5,ROM in spinal canal reconstruction group was similar to that in normal group(＜5％differ-ence),while ROM in laminectomy group was significantly higher than that in normal group and spinal canal reconstruction group(＞5％difference).In the overall maximum ROM of L3-L5,spinal canal reconstruction group was only slightly higher than normal group under the condition of posterior extension(＞5％difference),while laminectomy was significantly higher than normal group and spinal canal reconstruction group under the condition of anterior flexion,posterior extension,left and right rotation(＞5％difference).The changes of each segment ROM and overall ROM of L3-L5 showed laminectomy group＞spinal canal reconstruction group＞normal group.Conclusion Laminectomy could seriously affect biomechanical stability of the spine,but application of spinal canal reconstruction and internal fixation could effectively reduce ROM displacement of the responsi-ble segment of spine and maintain its biomechanical stability.

Objective This study aimed to investigate the effect and underlying mechanism of Fructus lycii in improving exercise fatigue.Methods A network pharmacological approach was used to explore potential mechanisms of action of Fructus lycii. Skeletal muscle C2C12 cells and immunofluorescence were employed to verify the effect and mechanism of the representative components in Fructus lycii predicted by network pharmacological analysis.Results Six potential active components, namely quercetin, β-sitosterol, stigmasterol, 7-O-methylluteolin-6-C-beta-glucoside_qt, atropine, and glycitein, were identified to have potency in improving exercise fatigue via multiple pathways, such as the PI3K-Akt, neuroactive ligand-receptor interaction, IL-17, TNF, and MAPK signaling pathways. The immunofluorescence results indicated that quercetin, a significant active component in Fructus lycii, increased the mean staining area of 2-NBDG, TMRM, and MitoTracker, and decreased the area of CellRox compared to the control. Furthermore, the protein expression levels of p-38 MAPK, p-MAPK, p-JNK, p-PI3K, and p-AKT markedly increased after quercetin treatment.Conclusion Fructus lycii might alleviate exercise fatigue through multiple components and pathways. Among these, quercetin appears to improve exercise fatigue by enhancing energy metabolism and reducing oxidative stress. The PI3K-AKT and MAPK signaling pathways also appear to play a role in this process.

Liver size is regulated by circadian clock and exhibits a diurnal rhythm. Pregnane X receptor (PXR) and peroxisome proliferator-activated receptor α (PPARα), members of nuclear receptor superfamily, are important regulators of liver size. We previously demonstrated that mPXR agonist pregnenolone 16α-carbonitrile (PCN) and mPPARα agonist pirinixic acid (WY-14643) promoted liver enlargement and liver regeneration after partial hepatectomy. However, whether PXR or PPARα activation-induced liver enlargement exhibits diurnal rhythm with normal liver diurnal oscillations remains unclear. The aim of this study was to investigate the diurnal rhythm of PXR or PPARα activation-induced liver enlargement. Male C57BL/6 mice were intraperitoneally injected with corn oil, PCN or WY-14643 for three days, and liver samples were weighed and collected at various time points for analysis. The animal experiment protocol was reviewed and approved by Institutional Animal Care and Use Committee of Sun Yat-sen University (approval No. SYSU-IACUC-2023-001613, SYSU-IACUC-2023-001783). The results showed that PXR or PPARα activation at various time points significantly induced liver enlargement, and liver size maintained normal diurnal oscillations during PXR or PPARα activation-induced hepatomegaly, without significant effects on the expression of core clock genes. This study reveals PXR or PPARα activation-induced liver enlargement exhibits diurnal rhythm with normal liver diurnal oscillations, and provides novel data for nuclear receptor-induced liver enlargement and liver diurnal rhythm.

Aim To explore the effects of Huannao Yicong decoction(HYD)on the learning and memory ability and brain iron metabolism in APP/PS1 mice and the correlation of HAMP knockout mice and APP/PS1 double transgenic model mice.Methods The ex-periment was divided into five groups,namely,HAMP-/-group(6-month HAMP gene knockout mice),APP/PS1 group(6-month APP/PS1-double-transgenic mice),HAMP-/-+HYD,APP/PS1+HYD,and negative control group(6-month C57BL/6J mice),with six mice in each group.The dose was ad-ministered(13.68 g·kg-1 weight),and the other groups received distilled water for gavage once a day for two months.After the administration of the drug,the mice in each group were tested for learning and memory in the Morris water maze;Biochemical detec-tion was performed to detect iron ion content in each mouse brain;Western blot and RT-qPCR were carried out to analyze hippocampal transferrin(TF),transfer-rin receptor1(TFR1),membrane iron transporter1(FPN1)divalent metal ion transporter 1(DMT1)and β-amyloid protein(Aβ)protein and mRNA expression levels in each group.Results Compared with the normal group,both HAMP-/-mice and APP/PS1 mice had reduced the learning and memory capacity,in-creased iron content in brain tissue,Aβ protein ex-pression increased in hippocampus of HAMP-/-group and APP/PS1 group mice(P＜0.01),the protein and mRNA expression of TF,TFR1 and DMT1 increased in hippocampal tissues of HAMP-/-and APP/PS1 groups(P＜0.01),and the FPN1 protein and mRNA expres-sion decreased(P＜0.01).Compared with the HAMP-and APP/PS1 groups,respectively,HAMP-/-+HYD group and APP/PS1+HYD group had improved learning and memory ability,decreased iron content,decreased Aβ protein expression(P＜0.01),decreased TF,TFR1,DMT1 protein and mR-NA expression(P＜0.01),and increased expression of FPN1 protein and mRNA(P＜0.01).Conclusions There is some association between HAMP-/-mice and APP/PS1 mice,HYD can improve the learning and memory ability of HAMP-/-and APP/PS1 mice and reduce the Aβ deposition.The mechanism may be related to the regulation of TF,TFR1,DMT1,FPN1 expression and improving brain iron overload.

Objective To investigate the role of magnesium ion(Mg2+)in cisplatin-induced acute kidney injury(Cis-AKI)in kidney organoids and HK-2 cells,as well as the potential mechanism.Methods Initially,we utilized human-derived induced pluripotent stem cells(iPSCs)to construct kidney organoids,and then built a Cis-AKI model based on kidney organoids.HE staining was used to observe the structure of kidney organoids,and immunofluorescence staining was used to observe the localization of markers and the expression of cleaved caspase-3.qRT-PCR was conducted to detect mRNA levels of tubular and glomerular markers,as well as inflammatory factors.Subsequently,the kidney organoids were randomly divided into control group,cisplatin group(Cis group),and Mg2+pretreatment group(Cis+Mg2+group).CCK-8 and ATP content assays were employed to evaluate the cell viability of renal tubular epithelial cells.TUNEL staining was performed to detect the apoptosis of renal tubular epithelial cells.Western blot was utilized to detect the expression of apoptosis-associated proteins(Bcl-2,Bax,cleaved caspase-3)and organic cation transporter 2(OCT2).Immunofluorescence was used to detect the localization and expression of OCT2.Results On the 10th day,the tubular structure in kidney organoids was visible,with abundant expression of renal markers.Treatment with 10 μmol/L cisplatin resulted in structural damage to kidney organoids,significantly increased expression of cleaved caspase-3 and mRNA levels of inflammatory factors,and significantly decreased ATP content.Compared with the Cis group,the Cis+Mg2+group showed increased ATP content in kidney organoids,reduced number of TUNEL-positive cells,significantly decreased expression of apoptosis-associated proteins,and significantly decreased expression of OCT2.However,there was no significant improvement in HK-2 cell viability,the number of TUNEL-positive cells,or apoptosis-associated proteins in the Cis+Mg2+group,and HK-2 cells did not express OCT2.Conclusion Kidney organoid is an ideal in vitro model to study the pathogenesis and treatment of Cis-AKI.Mg2+pretreatment can significantly reduce the damage of kidney organoids induced by cisplatin,and the mechanism may be related to the downregulation of OCT2.